Cytomegalovirus (CMV) is a herpesvirus which causes severe immunosuppression in the adult human or murine host during an acute infection. The virus primarily depresses cell-mediated immunity, including the cytotoxic T lymphocyte (CTL) response to tumor cells. The mechanism of CTL suppression is unknown, but evidence suggests that it may involve a perturbation of regulatory immune functions, most likely through the generation of a suppressor cell and/or factor. The investigator proposes to utilize the knowledge and techniques of the well-characterized cell-mediated response to the simian virus 40 (SV40) tumor rejection antigen as a means of defining alterations in cell-mediated immunity during an acute CMV infection. The effects of CMV on the early stage of CTL development will be quantitated by determining the frequency of CTL precursors activated in limiting dilution cultures of spleen or lymph node cells from CMV-infected mice. Virus-induced suppressor cells which may influence CTL development will be identified and quantitated. The suppressor cell(s) will also be characterized with respect to genetic restriction, phenotype, and ability to suppress both the differentiation of CTL precursors and the cytotoxic activity of effector CTL. The direct effect of a CMV infection on immunoregulatory cells required for activation and differentiation of CTL precursors will also be examined. Macrophages infected with CMV in vitro will be tested for interluekin-1 production and expression of Ia antigen important in antigen presentation. Interleukin-2 production by T helper lymphocytes from CMV-infected and noninfected mice will be quantitated and compared. Finally, the possibility that CMV directly interferes with the cytolytic activity of mature CTL will also be explored. The results from these experiments will provide the fundamental knowledge of the mechanism of CMV-induced suppression of tumor immunity necessary for future studies of specific virus-cell interactions.